1. Field of the Invention
The present invention relates to photoplethysmographic readings for animal research and more particularly, the present invention is directed to a noninvasive photoplethysmographic sensor platform for mobile animals such as small rodents.
2. Background Information
A photoplethysmograph is an optically obtained plethysmograph, which, generically, is a measurement of changes in volume within an organ whole body, usually resulting from fluctuations in the amount of blood or air that the organ contains. A photoplethysmograph is often obtained by using a pulse oximeter. A conventional pulse oximeter monitors the perfusion of blood to the dermis and subcutaneous tissue of the skin. Pulse oximetry is a non invasive method that allows for the monitoring of the oxygenation of a subject's blood, generally a human or animal patient or an animal (or possibly human) research subject. The patient/research distinction is particularly important in animals where the data gathering is the primary focus, as opposed to care giving, and where the physiologic data being obtained may, necessarily, be at extreme boundaries for the animal.
As a brief history of pulse oximetry, it has been reported that in 1935 an inventor Matthes developed the first 2-wavelength earlobe O2 saturation meter with red and green filters, later switched to red and infrared filters. This was the first device to measure O2 saturation. Further in 1949 an inventor Wood added a pressure capsule to squeeze blood out of the earlobe to obtain zero setting in an effort to obtain absolute O2 saturation value when blood was readmitted. The concept is similar to today's conventional pulse oximetry but suffered due to unstable photocells and light sources and the method was not used clinically. In 1964 an inventor Shaw assembled the first absolute reading ear oximeter by using eight wavelengths of light which was commercialized by Hewlett Packard. This use was limited to pulmonary functions due to cost and size. Effectively, modern pulse oximetry was developed in 1972, by Aoyagi at Nihon Kohden using the ratio of red to infrared light absorption of pulsating components at the measuring site, and this design was commercialized by BIOX/Ohmeda in 1981 and Nellcor, Inc. in 1983. Prior to the introduction of these commercial pulse oximeters, a patient's oxygenation was determined by a painful arterial blood gas, a single point measure which typically took a minimum of 20-30 minutes processing by a laboratory. It is worthy to note that in the absence of oxygenation, damage to the human brain starts in 5 minutes with brain death in a human beginning in another 10-15 minutes. Prior to its introduction, studies in anesthesia journals estimated US patient mortality as a consequence of undetected hypoxemia at 2,000 to 10,000 deaths per year, with no known estimate of patient morbidity. Pulse oximetry has become a standard of care for human patients since about 1987.
Pulse oximetry has been a critical research tool for obtaining associated physiologic parameters in humans and animals beginning soon after rapid pulse oximetry became practical.
In pulse oximetry a sensor is placed on a thin part of the subject's anatomy, such as a human fingertip or earlobe, or in the case of a neonate, across a foot, and two wavelengths of light, generally red and infrared wavelengths, are passed from one side to the other. Changing absorbance of each of the two wavelengths is measured, allowing determination of the absorbance due to the pulsing arterial alone, excluding venous blood, skin, bone, muscle, fat, etc. Based upon the ratio of changing absorbance of the red and infrared light caused by the difference in color between oxygen-bound (bright red) and oxygen unbound (dark red or blue, in severe cases) blood hemoglobin, a measure of oxygenation (the per cent of hemoglobin molecules bound with oxygen molecules) can be made.
The measured signals of pulse oximeters are also utilized to determine other physical parameters of the subjects, such as heart rate (pulse rate). Starr Life Sciences, Inc. has utilized pulse oximetry measurements to calculate other physiologic parameters such as breath rate, pulse distension, and breath distention, which can be particularly useful in various research applications.
Regarding human and animal pulse oximetry, the underlying theory of operation remains the same. However, consideration must be made for the particular subject or range of subjects in the design of the pulse oximeter, for example the sensor must fit the desired subject (e.g., a medical pulse oximeter for an adult human finger simply will not adequately fit onto a mouse finger or paw; and regarding signal processing the signal areas that are merely noise in a human application can represent signals of interest in animal applications due to the subject physiology). Consequently there can be significant design considerations in developing a pulse oximeter for small mammals or for neonates or for adult humans, but, again the underlying theory of operation remains substantially the same.
In addressing animal pulse oximetry, particularly for small rodents, one approach has been to modify existing human or neonate oximeters for use with rodents. This approach has proven impractical as the human based systems can only stretch so far and this approach has limited the use of such adapted oximeters. For example, these adapted human oximeters for animals have an upper limit of heart range of around 400 or 450 beats per minute which is insufficient to address mice that have a conventional heart rate of 400-800 beats per minute. Starr Life Sciences has designed a small mammal oximeter from the ground up, rather than an adapted human model, that has effective heart rate measurements up to 900 beats per minute, and this is commercially available under the Mouse Ox™ oximeter brand since 2005.
In the field of pulse oximetry in humans, U.S. Pat. No. 5,005,573 discloses an oximetry device in an endotracheal tube to enable “more accurate” and “more quickly responsive” oximetry measurements to be made through the patient's neck an to enable continual monitoring of the tube position within the trachea. Although this placement can provide improved oximetry measurements, it is much more invasive than conventional external pulse oximeters that have been placed on human fingers, toes and earlobes. Futher, endotracheal tube placement is impractical or mobile animal studies and for studies of small animals such as rodents (e.g. mice and rats).
U.S. Pat. No. 4,572,197 discloses a vest for positioning medical instrumentation about the human or, in theory, animal torso to provide ambulatory monitoring of patient cardiac functions.
In animal fields, neck collars have served as a mounting platform for selected sensors, such as bark sensors or position sensors in animal control collars that direct a pressure pulse wave to an animal as a negative stimulus to deter undesired behavior (e.g. shock), such as described in U.S. Pat. No. 6,830,013. Other animal control collars use a collar mounted sensor sensing a perimeter wire for animal control, see U.S. Pat. No. 6,657,544 and also products sold under the Invisible Fence® brand name.
In wildlife research, collars are the most common form of transmitter attachment for mammals in radio-telemetry studies, often wildlife studies. The following discussion offers background information on such radio-telemetry collar mounting considerations. Collars should be made of materials which are durable; are comfortable and safe for the animal; can withstand extreme environmental conditions; do not absorb moisture; and maintain their flexibility in low temperatures. Common collar materials for transmitter mounting in radio-telemetry based studies are butyl belting, urethane belting, flat nylon webbing, tubular materials, metal ball-chains, PVC plastic, brass or copper wire and cable ties. The transmitter package may be situated either under the animal's neck or on top of it. Collars must be properly fitted for the comfort and safety of the animal. A collar should fit snugly to prevent it coming off or chafing the animal as it moves, but it must also be sufficiently loose as to be comfortable and not interfere with swallowing or panting. To reduce the risk of chafing on the neck, collars should generally be fastened at the side, with any metal fittings covered or smoothed on the inside surface of the collar. Neck circumference will vary according to species, age, sex and sometimes the season. Transmitter manufacturers usually have records of collar sizes previously used for various species. Collar thickness and width are important considerations. Width of the collar will affect how the transmitter sits on the animal's neck. Some researchers prefer narrower collars because there is less surface area in contact with the animal. Others prefer wider collars for better weight distribution. One of the most important considerations should be the possibility of the collar getting caught up in vegetation. This is a particularly important consideration with small mammals (especially those that burrow). Expandable collars and harnesses are mandatory in those cases where it is necessary to allow for growth in young animals or for species which undergo neck swelling. Braided nylon over surgical tubing and nylon web with elastic folds are offered as expandable collars by one company. Expandable collars should not be used unless they are well tested, as poorly designed collars can be very problematic. In the past, certain collars have stretched prematurely as a result of social interactions or behaviors such as neck rubbing. As a result, there is always the possibility of transmitter loss, icing up in winter, or of the collar becoming snagged by branches or even the animal's own legs. Breakaway or “rot-away” collars are strongly recommended in cases where the researcher does not intend to recapture the animal and remove the collar. Breakaway collars or harnesses incorporate a link of material which is designed to break away and allow the transmitter to drop off after a pre-determined interval. Breakaway links should be environmentally degradable material or electronic links controlled by timers or radio receivers. Environmentally degradable materials which have been used for this purpose include cotton thread and sections of cotton fire hose or cotton spacers on large mammal collars. These weak links may also function to break and free the animal if the collar/harness is snagged on a branch. However, it is important to consider that the breakaway collar or harness does not impair the movement or activities of the animal during the period in which it is being shed. For example, a breakaway bird body harness could easily impair wing movement as it is lost and result in mortality. Radio and timer-controlled breakaways may be jammed by freezing or dirt, and also add to the size, weight and complexity of the transmitter package. Where appropriate, it is recommended that collars and harnesses be marked in order to enhance their visibility. Paint or non-metallic reflective materials may be sewn or glued to collars and harnesses; however, this is likely not appropriate for cryptic species. Metallic tape or foils should not be used as they will detune the transmitting antenna. Adhesive tapes should also not be used as they are not very durable and may foul fur or feathers. For game species or urban studies it may also be helpful to mark a contact phone number on the collar. Color-coded collars are also available from telemetry equipment manufacturers. VHF temperature sensors may be used to monitor either the animal's body temperature or the environmental temperature. Body temperature data may be useful in determining health or reproductive status, and ambient temperature may also be utilized for habitat selection or hibernation studies. Transmitters for body temperature may be placed subcutaneously, internally, within the inner ear, anally, or vaginally. Transmitters for ambient or den temperature may be placed on a regular collar or harness. Size or weight limitations and the data precision required will also affect transmitter type and placement.
A 2003 study at Kansas State University entitled “Wearable Sensor System for Wireless State-of-Health Determination in Cattle” disclosed a collection of sensors for animal research which was designed to incorporate off-the-shelf and custom-designed sensors and modules to provide cost-effective animal health monitoring capabilities. These sensors and modules included a GPS (Global Positioning System) unit, a pulse oximeter, a core body temperature sensor, an electrode belt, a respiration transducer, and an ambient temperature transducer. A GPS collar unit was intended to yield both animal location and movement data. A commercial CorTemp system was intended to monitors core body temperature continuously via an ingestible bolus. The bolus wirelessly transmitted temperature data to a receiving unit connected to BMOO. The animal was also to wear a Polar electrode belt that acquires pulse rate and transmits it wirelessly to the core body temperature receiving unit. A custom-designed pulse oximeter was proposed to measure blood oxygen saturation and pulse rate from an ear tag that the animal would wear. It is interesting to note that in this attempt for pulse oximetry in cattle, off the shelf human oximeters, were insufficient and a custom design was required.
Some invasive sensor proposals have been made for animal research including U.S. Patent Application Publication No. 2002-0010390 that discloses an Automated Animal Health Monitoring System (AAHMS) for automated monitoring and early warning of changes in parameters related to the health and status of animals. The system includes implantable wireless “smart tele-sensor” elements that can be implanted within the animal where they measure, and may transmit, temperature and other parameters (e.g., blood oxygen, accelerations, vibrations, heart rate) related to the health and status of the animal being monitored. Optional relay elements may comprise simple transponders to boost the signals from the smart sensor elements and retransmit processed results. The system includes devices for alerting personnel responsible for care of the animals and identifying the animal needing attention. Installation tools include optional capabilities to program the smart sensor elements to adapt to animal type, season, diet, or other user needs, and to read and correlate electronic and machine read data with human readable animal identification (e.g., ear or collar tags).
None of the above solutions adequately address laboratory animal research applications using mobile animals and more particularly, the prior art fails to adequately provide and efficient a noninvasive photoplethysmographic sensor platform for mobile animals such as small rodents, namely rats and mice.
It is an object of the present invention to address the deficiencies of the prior art discussed above and to do so in an efficient, cost effective manner.